List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Serum albumin level. The EFO term serum albumin measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
N Franceschini, FJ van Rooij, BP Prins, MF Feitosa, M Karakas, JH Eckfeldt, AR Folsom, J Kopp, A Vaez, JS Andrews, J Baumert, V Boraska, L Broer, C Hayward, JS Ngwa, Y Okada, O Polasek, HJ Westra, YA Wang, F Del Greco M, NL Glazer, K Kapur, IP Kema, LM Lopez, A Schillert, AV Smith, CA Winkler, L Zgaga, S Bandinelli, S Bergmann, M Boban, M Bochud, YD Chen, G Davies, A Dehghan, J Ding, A Doering, JP Durda, L Ferrucci, OH Franco, L Franke, G Gunjaca, A Hofman, FC Hsu, I Kolcic, A Kraja, M Kubo, KJ Lackner, L Launer, LR Loehr, G Li, C Meisinger, Y Nakamura, C Schwienbacher, JM Starr, A Takahashi, V Torlak, AG Uitterlinden, V Vitart, M Waldenberger, PS Wild, M Kirin, T Zeller, T Zemunik, Q Zhang, A Ziegler, S Blankenberg, E Boerwinkle, IB Borecki, H Campbell, IJ Deary, TM Frayling, C Gieger, TB Harris, AA Hicks, W Koenig, CJ O' Donnell, CS Fox, PP Pramstaller, BM Psaty, AP Reiner, JI Rotter, I Rudan, H Snieder, T Tanaka, CM van Duijn, P Vollenweider, G Waeber, JF Wilson, JC Witteman, BH Wolffenbuttel, AF Wright, Q Wu, Y Liu, NS Jenny, KE North, JF Felix, BZ Alizadeh, LA Cupples, JR Perry, AP Morris
List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Serum total protein level. The EFO term total blood protein measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
N Franceschini, FJ van Rooij, BP Prins, MF Feitosa, M Karakas, JH Eckfeldt, AR Folsom, J Kopp, A Vaez, JS Andrews, J Baumert, V Boraska, L Broer, C Hayward, JS Ngwa, Y Okada, O Polasek, HJ Westra, YA Wang, F Del Greco M, NL Glazer, K Kapur, IP Kema, LM Lopez, A Schillert, AV Smith, CA Winkler, L Zgaga, S Bandinelli, S Bergmann, M Boban, M Bochud, YD Chen, G Davies, A Dehghan, J Ding, A Doering, JP Durda, L Ferrucci, OH Franco, L Franke, G Gunjaca, A Hofman, FC Hsu, I Kolcic, A Kraja, M Kubo, KJ Lackner, L Launer, LR Loehr, G Li, C Meisinger, Y Nakamura, C Schwienbacher, JM Starr, A Takahashi, V Torlak, AG Uitterlinden, V Vitart, M Waldenberger, PS Wild, M Kirin, T Zeller, T Zemunik, Q Zhang, A Ziegler, S Blankenberg, E Boerwinkle, IB Borecki, H Campbell, IJ Deary, TM Frayling, C Gieger, TB Harris, AA Hicks, W Koenig, CJ O' Donnell, CS Fox, PP Pramstaller, BM Psaty, AP Reiner, JI Rotter, I Rudan, H Snieder, T Tanaka, CM van Duijn, P Vollenweider, G Waeber, JF Wilson, JC Witteman, BH Wolffenbuttel, AF Wright, Q Wu, Y Liu, NS Jenny, KE North, JF Felix, BZ Alizadeh, LA Cupples, JR Perry, AP Morris
List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Metabolite levels. The EFO term serum albumin measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
YJ Kim, MJ Go, C Hu, CB Hong, YK Kim, JY Lee, JY Hwang, JH Oh, DJ Kim, NH Kim, S Kim, EJ Hong, JH Kim, H Min, Y Kim, R Zhang, W Jia, Y Okada, A Takahashi, M Kubo, T Tanaka, N Kamatani, K Matsuda, T Park, B Oh, K Kimm, D Kang, C Shin, NH Cho, HL Kim, BG Han, JY Lee, YS Cho
Ethanol Induced Hypothermia Chr# 7 rs13479153(25722935) with right flanking marker rs3700068(4187548) and left marker rs3716088(140189839). This was mapped in 300 + (b6x129)F2 mice.
Average rotarod training latency Chr# 7 mCV23423763(68111945) with right flanking marker rs3700068(4187548) and left marker rs3663988(146505067). This was mapped in 300 + (b6x129)F2 mice.
Microglia depletion and alcohol gene expression logFC
Description:
Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here, we determine microglia function in acute and voluntary drinking behaviors using a colony-stimulating factor 1 receptor inhibitor (PLX5622). We show that microglia depletion does not alter the sedative or hypnotic effects of acute intoxication. Microglia depletion also does not change the escalation or maintenance of chronic voluntary alcohol consumption. Transcriptomic analysis revealed that although many immune genes have been implicated in alcohol abuse, down regulation of microglia genes does not necessitate changes in alcohol intake. Instead, microglia depletion and chronic alcohol result in compensatory upregulation of alcohol-responsive, reactive astrocyte genes, indicating astrocytes may play a role in regulation of these alcohol behaviors. Taken together, our behavioral and transcriptional data indicate that microglia are not theprimary effector cell responsible for regulation of acute and voluntary alcohol behaviors. Because microglia depletion did not regulate acute or voluntary alcohol behaviors, we hypothesized that these doses were insufficient to activate microglia and recruit them to an effector phenotype. Therefore, we used a model of repeated immune activation using polyinosinic:polycytidylic acid
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Alcohol dependence in the medial prefrontal cortex q-value
Description:
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Alcohol interaction of dependence and MG depletion the medial prefrontal cortex q-value
Description:
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue
Description:
To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.
Authors:
Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler
Affymetrix oligonucleotide arrays to assess gene expression in brains of mice selectively bred for differences in acute functional tolerance to an incoordinating effect of ethanol (HAFT mice, high acute functional tolerance; LAFT mice, low acute functional tolerance)
This gene set comprises 239 genes that are differentially expressed within each of five brain regions (amygdala, hippocampus, nucleus accumbens, prefrontal cortex and ventral tegmental area) when chronic nicotine treatment is administered to C57BL/6J mice only. Background: Studies involving use of chronic nicotine treatment identify unique nicotine addiction genes and the biological processes they control in B6 and C3 mice. Results are obtained using gene expression profiling and gene ontology.
Authors:
Wang J, Gutala R, Hwang YY, Kim JM, Konu O, Ma JZ, Li MD
Striatum Gene Expression Correlates for ST_PCT_PPI_70 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_PPI_70 measures Prepulse inhibition at 70db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Striatum Gene Expression Correlates for ST_PCT_STARTLE_70 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_STARTLE_70 measures Acoustic Startle Response Percentage of maximum startle response at 70 db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Hippocampus Gene Expression Correlates for ZM_ACTIVITY measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ZM_ACTIVITY measures Zero Maze - Total Activity count; number of beam breaks under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Hippocampus Gene Expression Correlates for ENTRIES_CLOSED measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for LM_PAIR1 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PAIR1 measures Activity during 1st tone shock pairing under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for MDMA_ACT_MDA_1 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The MDMA_ACT_MDA_1 measures Locomotor response of 10 mg/kg MDMA injected on Day 2 under the domain MDMA. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Grice DE, Reenil I, Mnnist PT, Brooks AI, Smith GG, Golden GT, Buxbaum JD, Berrettini WH
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